Alkynyl gold(I) phosphane complexes

• Verfasst von: Andermark, Vincent [VerfasserIn]
• Verfasst von: Göke, Katrin [VerfasserIn]
• Verfasst von: Kokoschka, Malte [VerfasserIn]
• Verfasst von: Abu El Maaty, Mohamed A. [VerfasserIn]
• Verfasst von: Lum, Ching Tung [VerfasserIn]
• Verfasst von: Zou, Taotao [VerfasserIn]
• Verfasst von: Sun, Raymond Wai-Yin [VerfasserIn]
• Verfasst von: Aguiló, Elisabet [VerfasserIn]
• Verfasst von: Oehninger, Luciano [VerfasserIn]
• Verfasst von: Rodríguez, Laura [VerfasserIn]
• Verfasst von: Bunjes, Heike [VerfasserIn]
• Verfasst von: Wölfl, Stefan [VerfasserIn]
• Verfasst von: Che, Chi-Ming [VerfasserIn]
• Verfasst von: Ott, Ingo [VerfasserIn]
• Titel: Alkynyl gold(I) phosphane complexes
• Titelzusatz: evaluation of structure-activity-relationships for the phosphane ligands, effects on key signaling proteins and preliminary in-vivo studies with a nanoformulated complex
• Verf.angabe: Vincent Andermark, Katrin Göke, Malte Kokoschka, Mohamed A. Abu el Maaty, Ching Tung Lum, Taotao Zou, Raymond Wai-Yin Sun, Elisabet Aguiló, Luciano Oehninger, Laura Rodríguez, Heike Bunjes, Stefan Wölfl, Chi-Ming Che, Ingo Ott
• Jahr: 2016
• Jahr des Originals: 2015
• Umfang: 9 S.
• Fussnoten: Available online 30 December 2015 ; Gesehen am 17.08.2020
• Titel Quelle: Enthalten in: Journal of inorganic biochemistry
• Ort Quelle: New York, NY [u.a.] : Elsevier, 1979
• Jahr Quelle: 2016
• Band/Heft Quelle: 160(2016), Seite 140-148
• ISSN Quelle: 1873-3344
• DOI: doi:10.1016/j.jinorgbio.2015.12.020
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Alkyne
• Sach-SW: Cancer
• Sach-SW: Formulation
• Sach-SW: Gold
• Sach-SW: Microarray
• Sach-SW: Xenograft
• K10plus-PPN: 1727161602

Abstract

Gold alkynyl complexes with phosphane ligands of the type (alkynyl)Au(I)(phosphane) represent a group of bioorganometallics, which has only recently been evaluated biologically in more detail. Structure-activity-relationship studies regarding the residues of the phosphane ligand (P(Ph)3, P(2-furyl)3, P(DAPTA)3, P(PTA)3, P(Et)3, P(Me)3) of complexes with an 4-ethynylanisole alkyne ligand revealed no strong differences concerning cytotoxicity. However, a relevant preference for the heteroatom free alkyl/aryl residues concerning inhibition of the target enzyme thioredoxin reductase was evident. Complex 1 with the triphenylphosphane ligand was selected for further studies, in which clear effects on cell morphology were monitored by time-lapse microscopy. Effects on cellular signaling were determined by ELISA microarrays and showed a significant induction of the phosphorylation of ERK1 (extracellular signal related kinase 1), ERK2 and HSP27 (heat shock protein 27) in HT-29 cells. Application of 1 in-vivo in a mouse xenograft model was found to be challenging due to the low solubility of the complex and required a formulation strategy based on a peanut oil nanoemulsion.